Preparation, characterization, and screening of a high affinity organometallic probe for α-adrenergic receptors

An organometallic rhenium complex having high and selective affinity for α-adrenergic receptors is reported. A series of methoxyphenylpiperazinecarborane ligands complexed to the [Re(CO)(3)](+) core were prepared and the resulting organometallic compounds screened for binding to serotonin, σ, and adrenergic receptors as well as dopamine, serotonin, and norepinephrine transporters. An amide linked derivative, for which a single crystal X-ray structure was obtained, showed high and selective affinity toward α(1A), α(1D), and α(2C) adrenergic receptors with K(i) values of 17, 21, and 39 nM, respectively. A method to prepare the corresponding (99m)Tc complex was also developed where the resulting metallocarborane was shown to be stable and is therefore suitable for in vivo molecular imaging studies.